Contact

Department

Cellular and Integrative Physiology

Sijia He, Ph.D.

Assistant Professor (Research)

Education

Ph.D., Physiology & Pharmacology, UTHealth San Antonio, United States
M.S., Biomedical Science, Hunan University, China
B.S., Bioinformatics, Huazhong University of Science & Technology, China

Research

We are focused on identifying novel factors and mechanisms involved in aging and neurodegeneration. Our recent studies primarily concentrate on the following areas:

1.    The role of lipids in aging and neurodegeneration. The central nervous system (CNS) is highly enriched in lipids, which are critical for maintaining cellular integrity, signaling, and energy homeostasis. Disruptions in CNS lipid homeostasis have been observed in both aging and neurodegenerative conditions; however, the impact of these alterations on aging and disease progression remains poorly understood. To investigate these dynamics, we employ lipidomics to identify specific lipid species changes associated with aging and disease. These observations guide further research to determine the underlying factors that trigger these lipid changes and to uncover the signaling and functional pathways affected by lipid alterations. We use both in vitro cell culture and in vivo mouse models to elucidate the role of key lipids in aging and neurodegeneration, aiming to clarify their involvement in disease mechanisms and potential therapeutic implications.

2.    Innate immune-associated disease mechanisms in Alzheimer’s disease (AD). Innate immune activation plays a crucial role in the pathogenesis of AD and AD related dementias (ADRD). The cytosolic DNA sensing pathway, involving cGAMP synthase (cGAS) and Stimulator of Interferon Genes (STING), has emerged as a key mediator in neurodegenerative disease progression. Our recent work has identified microglia as a major contributor to elevated cGAS levels in the AD brain. Using a microglia-specific cGAS deficient mouse model, we demonstrated that reducing microglial cGAS-mediated innate immune response profoundly limited amyloid-β (Aβ) pathology and protected mice from Aβ-induced cognitive impairment. Currently, we are employing single-cell sequencing techniques to examine the effects of innate immune modulation at single-cell resolution, aiming to further elucidate cellular and molecular mechanisms associated with the change of innate immune status. This research is essential for understanding the bidirectional relationship between immune activation and neuronal health, offering potential targets for modulating the innate immune system as a therapeutic intervention in AD.

Publications

For a complete list of published work, please visit MyBibliography: https://www.ncbi.nlm.nih.gov/myncbi/sijia.he.2/bibliography/public/

1.    Xu Z, He S (co-first author), Begum M and Han X. Myelin Lipid Alterations in Neurodegenerative Diseases: Landscape and Pathogenic Implications. Antioxid. Redox Signal. (2024)
2.    Zhao S, Li N, Xiong W, Li G, He S, Zhang Z, Zhu Q, et. al. Leptin Reduction as a Required Component for Weight Loss. Diabetes. 73(2):197-210. (2024) (PMCID: PMC10796304).
3.    He S, Qiu S, Pan M, Palavicini JP, Wang H, Li X, Bhattacharjee A, Barannikov S, Bieniek KF, Dupree JL and Han X. Marked Reduction of Spinal Cord Lipidome in Late Alzheimer’s Disease Contributes to Neurogenic Bladder. Clin. Transl. Med. 13(7):e1332. (2023) (PMCID: PMC10361545).
4.    Qiu S, He S (co-first author), Wang J, Wang H, Bhattacharjee A, Li X, Dupree JL  and Han X. Adult-onset CNS myelin sulfatide deficiency causes sex-dependent metabolic disruption during aging. Int. J. Mol. Sci. 24(13): 10483. (2023) (PMCID: PMC10341976).
5.    Qiu S, Palavicini JP, Wang J, Gonzalez NS, He S, Dustin E, Zou C, Ding L, Bhattacharjee A, VanSkike CE, Galvan V, Dupree JL, and Han X. Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer’s disease-like neuroinflammation and cognitive impairment. Mol. Neurodegener. 16(64). (2021) (PMCID: PMC8442347)
6.    Plasko G, He S, Zhang J, Liu F, Bai J, Dong LQ and Liu F. Deficiency of novel adipokine tetranectin increases obesity and insulin resistance in females. J Clin Transl Sci. 5(Suppl 1): 19. (2021)
7.    He S, Ryu J, Liu J, Luo H, Lv Y, Langlais PR, Wen J, Dong F, Sun Z, Xia W, Lynch JL, Duggirala R, Nicholson BJ, Zang M, Shi Y, Zhang F, Liu F, Bai J and Dong LQ. LRG1 is an adipokine that mediates obesity-induced hepatic steatosis and insulin resistance. J. Clin. Invest. 131(24):e148545. (2021) (PMCID: PMC8670837)
8.    Bai J, Cervantes C, He S, He J, Plasko RG, Wen J, Li Z, Yin D, Zhang C, Liu M, Dong LQ and Liu F. Mitochondrial stress-activated cGAS-STING pathway inhibits thermogenic program and contributes to overnutrition-induced obesity in mice. Commun. Biol. 3:257. (2020) (PMCID: PMC7244732)
9.    Bai J, Cervantes C, Liu J, He S, Zhou H, Zhang B, Cai H, Yin D, Hu D, Li Z, Chen H, Gao X, Wang F, O’Connor JC, Xu Y, Liu M, Dong LQ and Liu F. DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway. PNAS, 114(46) 12196-12201. (2017) (PMCID: PMC5699051)
10.    Meng W, Liang X, Chen H, Luo H, Bai J, Li G, Zhang Q, Xiao T, He S, Zhang Y, Xu Z, Xiao B, Liu M, Hu F and Liu F. Rheb Inhibits Beiging of White Adipose Tissue via PDE4D5-Dependent Downregulation of the cAMP-PKA Signaling Pathway. Diabetes. 66(5):1198-1213. (2017) (PMCID: PMC5860267)
11.    Liu M, Bai J, He S, Villarreal R, Hu D, Zhang C, Yang X, Liang H, Slaga TJ, Yu Y, Zhou Z, Blenis J, Sherer PE, Dong LQ and Liu F. Grb10 Promotes Lipolysis and thermogenesis by Phosphorylation- dependent Feedback Inhibition of mTORC1. Cell Metab. 19(6):967-80. (2014) (PMCID: PMC4064112)
12.    Chen T, He S, Zhang Z, Gao W, Yu L and Tan Y. Foxa1 contributes to the repression of Nanog expression by recruiting Grg3 during the differentiation of pluripotent P19 embryonal carcinoma cells. Exp. Cell. Res. 326(2):326-35. (2014) (PMID: 24803390)

 

Preprints:
13.    He S, Li X, Bhattacharjee A, Liu F and Han X. Microglial disruption of innate immune DNA sensing cGAS-STING pathway ameliorates amyloid-β pathology and improve cognitive function in Alzheimer’s disease. BioRxiv. Preprint. Version 1. 2023 Aug 8. (2023) (PMCID: PMC10441288)